BLOCKADE OF LEUKOCYTE FUNCTION-ASSOCIATED ANTIGEN (LFA-1) IN A MURINE MODEL OF LUNG INFLAMMATION
BLOCKADE OF LEUKOCYTE FUNCTION-ASSOCIATED ANTIGEN (LFA-1) IN A MURINE MODEL OF LUNG INFLAMMATION
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DOI：
10.1165/ajrcmb.10.5.8179910
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发表时间：
1994-05-01
影响因子：
6.4
通讯作者：
BISSON, D
中科院分区：
文献类型：
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作者：
DENIS, M;BISSON, D
我们研究了白细胞功能相关抗原（LFA-1）在小鼠肺部炎症模型中的作用，该模型是通过暴露于嗜热放线菌Faeni直肠状Faeni来确定的。从支气管肺泡灌洗（BAL）恢复的细胞数量增加和肺病变的组织学评分来看，暴露导致大量细胞涌入支气管肺泡间隙和肺实质。鼻内反复暴露于直线弧菌也导致肺羟脯氨酸水平显著增加。组织学分析显示，致毒小鼠肺部出现肺泡壁炎症，间质肿胀充血，上皮细胞破坏，肉芽肿偶见上皮样细胞。同时注射抗LFA-1大鼠抗体和抗原刺激的小鼠，BAL炎症细胞数量没有减少，但抗LFA-1治疗显著减少肺纤维化，通过肺羟脯氨酸水平评估；从形态学分析可以看出，实质炎症和组织损伤也明显减轻。发现抗lfa -1治疗已建立的过敏性肺炎小鼠可显著降低肺羟脯氨酸水平和组织损伤；BAL细胞数量未受影响。从这些结果，我们得出结论，过敏性肺炎的纤维化和组织损伤反应，而不是肺泡炎，部分依赖于lfa -1介导的细胞相互作用。此外，抗原诱导的肺组织病变的维持与LFA-1表达有关，基于抗LFA-1的干预可能在治疗已建立的肺纤维化方面有一些希望。
We examined the contribution of the leukocyte function-associated antigen (LFA-1) in a murine model of lung inflammation determined by exposure to the thermophilic actinomycete Faeni rectivirgula. The exposure generated a large influx of cells in the bronchoalveolar space and in the lung parenchyma, as seen from enhanced numbers of cells recovered by bronchoalveolar lavage (BAL) and histologic scoring of lung lesions. Repeated intranasal exposure to F. rectivirgula also resulted in a significant increase in lung hydroxyproline levels. Histologic analysis showed that alveolar wall inflammation, interstitial swelling and congestion, epithelial cell destruction, and granulomas with occasional epithelioid cells were observed in the lungs of challenged mice. Mice injected with rat antibodies against LFA-1 concomitantly with an antigen challenge showed no reduction in the number of BAL inflammatory cells, but lung fibrosis was significantly reduced by anti-LFA-1 treatment as assessed by lung hydroxyproline levels; parenchymal inflammation and tissue damage were also significantly reduced as seen from morphometric analysis. Anti-LFA-1 treatment of mice with established hypersensitivity pneumonitis was found to significantly reduce the levels of lung hydroxyproline and tissue damage; the numbers of BAL cells remained unaffected. From these results, we conclude that the fibrosis and tissue-damaging reactions in hypersensitivity pneumonitis, but not the alveolitis, are partly dependent on LFA-1-mediated cellular interactions. Moreover, the maintenance of lung tissue lesions induced by antigens is linked to LFA-1 expression, and anti-LFA-1-based intervention may hold some promise in the treatment of established lung fibrosis.